Citric acid cycle acetyl coenzyme

Acetyl CoA carries two-carbon remnants of the nutrients, acetyl groups, to the citric acid cycle. Acetyl CoA enters the cycle, and electrons and hydrogen atoms are harvested during the complete oxidation of the acetyl group to CO2. Coenzyme A is released (recycled) to carry additional acetyl groups to the pathway. The electrons and hydrogen atoms that are harvested are used in the process of oxidative phosphorylation to produce ATP. 

A fatty acid with an even number of carbons is metabolized to acetyl-CoA, which can then enter the citric acid cycle to be further metabolized (Section 25.10). A fatty acid with an odd number of carbons is metabolized to acetyl-CoA and one equivalent of propionyl-CoA. Propionyl-CoA cannot enter the citric acid cycle. Two coenzyme-requiring enzymes are needed to convert it into succinyl-CoA, a compound that can enter the citric acid cycle. Write the two enzyme-catalyzed reactions and include the names of the required coenzymes. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs tycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

Figure 29.12 MECHANISM The citric acid cycle is an eight-step series of reactions that results in the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes. Individual steps are explained in the text.

The citric acid cycle (Krebs cycle, tricarboxylic acid cycle) is a series of reactions in mitochondria that oxidize acetyl residues (as acetyl-CoA) and reduce coenzymes that upon reoxidation are linked to the formation of ATP. 

The citric acid cycle is an integral part of the process by which much of the free energy liberated during the oxidation of fuels is made available. During oxidation of acetyl-CoA, coenzymes are reduced and subsequendy reoxidized in the respiratory chain, hnked to the formation of ATP (oxicktive phosphorylation see Figure 16-2 and also Chapter 12). This process is aerobic, requiring oxygen as the final oxidant of the reduced coenzymes. The enzymes of the citric acid cycle are lo-... 

The citric acid cycle is the final pathway for the oxidation of carbohydrate, Upid, and protein whose common end-metabolite, acetyl-CoA, reacts with oxaloacetate to form citrate. By a series of dehydrogenations and decarboxylations, citrate is degraded, releasing reduced coenzymes and 2CO2 and regenerating oxaloacetate. 

Coenzyme A (CoA), 20 249—250. See also Ace to acetyl- Co A in citric acid cycle, 6 633 Coenzyme Q10, 17 673 Coercivity, ofM-type ferrites, 11 70 Coextruded food packaging, 18 44, 45 Coextrusion techniques, for gelatin capsule preparation, 11 549 Cofactors, 10 253 11 4 folic acid, 25 801-802 for enzymes, 3 672-673 protein, 20 828-829 vitamin B12, 25 804 vitamins as, 25 781 Coffea arabica, 7 250 Cojfea Canephora, 7 250 Coffea liberica, 7 250 Coffee, 2 108 6 366 7 250-271 biotechnology, 7 265-267 decaffeinated, 7 263 economic aspects, 7 263-264 estimated maximum oxygen tolerance, 3 381t... 

Chenoweth believes that an explanation of the above results may lie in the reactions occurring before the entrance of fatty acid metabolites into the citric acid cycle. Activated acetate, i.e. acetyl coenzyme A (AcCoA) is the end-product of fatty acid metabolism prior to its condensation with oxalacetate to form citrate. Possibly fluoro-fatty acids behave like non-fluorinated fatty acids. The end-product before the oxalacetate condensation could be the same for all three fluorinated inhibitors, viz. fluoroacetyl coenzyme A (FAcCoA). Fluorocitrate could then be formed by the condensation of oxalacetate with FAcCoA, thereby blocking the citric acid cycle. The specificity of antagonisms must therefore occur before entrance of the metabolites into the citric acid cycle. 

As noted earlier, coenzymes are frequently altered structurally in the course of an enzymatic reaction. However, they are usually reconverted to their original structure in a subsequent reaction, as opposed to being further metabolized. One turn of the citric acid cycle converts NAD+ into NADH, FAD into FADH2, and acetyl-SCoA into CoASH. Coenzyme A is consumed in the metabolism of pyruvate (see below) but regenerated in the citric acid cycle. Both NADH and FADH2 are reconverted into NAD+ and FAD by the electron transport chain. 

In this reaction, pyruvic acid is oxidized to carbon dioxide with formation of acetyl-SCoA and NAD+ is reduced to NADH. As noted in chapter 15, this reaction requires the participation of thiamine pyrophosphate as coenzyme. Here too the NADH formed is converted back to NAD+ by the electron transport chain. As noted above, the acetyl-SCoA is consumed by the citric acid cycle and CoASH is regenerated. 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

In examining the eight successive reaction steps of the citric acid cycle, we place special emphasis on the chemical transformations taking place as citrate formed from acetyl-CoA and oxaloacetate is oxidized to yield C02 and the energy of this oxidation is conserved in the reduced coenzymes NADH and FADH2. 

In extraliepatic tissues, d-/3-hydroxybutyrate is oxidized to acetoacetate by o-/3-hydroxybutyrate dehydrogenase (Fig. 17-19). The acetoacetate is activated to its coenzyme A ester by transfer of CoA from suc-cinyl-CoA, an intermediate of the citric acid cycle (see Fig. 16-7), in a reaction catalyzed by P-ketoacyl-CoA transferase. The acetoacetyl-CoA is then cleaved by thiolase to yield two acetyl-CoAs, which enter the citric acid cycle. Thus the ketone bodies are used as fuels. 

Conditions that promote gluconeogenesis(untreated diabetes, severely reduced food intake) dow the citric acid cycle (by drawing off oxaloacetate) and enhance the conversion of acetyl-CoA to acetoacetate. The released coenzyme A allows continued /3 oxidation of fatty acids... 

Polycarboxylic acid synthases. Several enzymes, including citrate synthase, the key enzyme which catalyzes the first step of the citric acid cycle, promote condensations of acetyl-CoA with ketones (Eq. 13-38). An a-oxo acid is most often the second substrate, and a thioester intermediate (Eq. 13-38) undergoes hydrolysis to release coenzyme A.199 Because the substrate acetyl-CoA is a thioester, the reaction is often described as a Claisen condensation. The same enzyme that catalyzes the condensation of acetyl-CoA with a ketone also catalyzes the second step, the hydrolysis of the CoA thioester. These polycarboxylic acid synthases are important in biosynthesis. They carry out the initial steps in a general chain elongation process (Fig. 17-18). While one function of the thioester group in acetyl-CoA is to activate the methyl hydrogens toward the aldol condensation, the subsequent hydrolysis of the thioester linkage provides for overall irreversibility and "drives" the synthetic reaction. 

While CoA was discovered as the "acetylation coenzyme," it has a far more general function. It is required, in the form of acetyl-CoA, to catalyze the synthesis of citrate in the citric acid cycle. It is essential to the P oxidation of fatty acids and carries propionyl and other acyl groups in a great variety of other metabolic reactions. About 4% of all known enzymes require CoA or one of its esters as a substrate.4... 

Acetyl CoA is oxidized in the citric-acid cycle to yield C02 and reduced coenzymes. 

The Krebs-citric acid cycle is the final common pathway for the oxidation of fuel molecules amino acids, fatty acids and carbohydrates. Most fuel molecules enter the cycle as a breakdown product, acetyl coenzyme A (acetyl CoA), which reacts with oxaloacetate (a four-carbon compound) to produce citrate (a six-carbon compound), which is then converted in a series of enzyme-catalysed steps back to oxaloacetate. In the process, two molecules of carbon dioxide and four energy-rich molecules are given off, and these latter are the precursors of the energy-rich molecule ATP, which is subsequently formed and which acts as the fuel source for all aerobic organisms. 

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